Characterization of PR-Cre Activity in the Testis and Its Application Reveals BRG1 Is Dispensable in Adult Leydig...

Leydig cells play a crucial role in male development, fertility, and overall health through hormone production. Brahma-related gene 1 (BRG1), the catalytic subunit of the mammalian SWI/SNF complex, is a key regulator of chromatin accessibility and governs the development and function of diverse tissues. However, its role in Leydig cells remains unclear. In this study, we first characterized the expression pattern of PR-Cre in the testes, as this Cre mouse line has been widely used for gene targeting in the female reproductive system, but its activity in the testis has never been systematically reported. We found that PR-Cre drives recombination in multiple testicular cell types, including stem/progenitor adult Leydig cells (ALCs), peritubular myoid cells, and elongated spermatids. Using PR-Cre to conditionally delete BRG1 in ALCs, we observed no detectable abnormalities in ALC development, spermatogenesis, or male fertility. Similar results were obtained using the Cyp17a1-iCre mouse line and AAV8-iCre viral delivery for BRG1 deletion. Collectively, this work demonstrates that BRG1 is dispensable for ALC development and function, while providing a comprehensive characterization of PR-Cre as a valuable new tool for male reproductive research.